Akaneya Y, Tsumoto T, Kinoshita S, Hatanaka H
Department of Neurophysiology, Biomedical Research Center, Osaka University Medical School, Suita City, 565 Japan.
J Neurosci. 1997 Sep 1;17(17):6707-16. doi: 10.1523/JNEUROSCI.17-17-06707.1997.
Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), members of the nerve growth factor (NGF) gene family, have been suggested to play a role in experience-dependent modification of neural networks in the developing nervous system. In this study we addressed the question of whether these neurotrophins are involved in long-term potentiation (LTP) in developing visual cortex. We recorded layer II/III field potentials and whole-cell currents evoked by test stimulation of layer IV at 0.1 Hz in visual cortical slices prepared from young rats (postnatal day 15-25) and observed effects of BDNF, NT-3, and NGF on these responses. Then we analyzed the effects of these neurotrophins on LTP induced by tetanic (Theta-burst type) stimulation of layer IV. We found that BDNF at 200 ng/ml potentiated field potentials and EPSCs in most cases and that this potentiation lasted after cessation of the BDNF application. At the concentration of 20 ng/ml, BDNF did not show such an effect, but it enhanced the magnitude of expressed LTP. On the other hand, NT-3 and NGF had none of these effects. Immunohistochemical staining of slices with antibody against BDNF showed that exogenous BDNF penetrated into the whole slice within approximately 5 min of its application. The actions of BDNF were blocked by preincubation of slices with TrkB-IgG fusion protein, a BDNF scavenger, or coapplication of K252a, an inhibitor for receptor tyrosine kinases. TrkB-IgG or K252a itself completely blocked LTP, suggesting that endogenous BDNF or another TrkB ligand plays a role in LTP in the developing visual cortex.
脑源性神经营养因子（BDNF）和神经营养素-3（NT-3）是神经生长因子（NGF）基因家族的成员，有人认为它们在发育中的神经系统神经网络的经验依赖性修饰中发挥作用。在本研究中，我们探讨了这些神经营养因子是否参与发育中的视觉皮层的长时程增强（LTP）。我们在从幼鼠（出生后第15 - 25天）制备的视觉皮层切片中，以0.1 Hz的频率对IV层进行测试刺激，记录II/III层的场电位和全细胞电流，并观察BDNF、NT-3和NGF对这些反应的影响。然后我们分析了这些神经营养因子对IV层强直（θ波爆发型）刺激诱导的LTP的影响。我们发现，200 ng/ml的BDNF在大多数情况下增强了场电位和兴奋性突触后电流（EPSCs），并且在停止应用BDNF后这种增强作用仍然持续。在20 ng/ml的浓度下，BDNF没有显示出这种作用，但它增强了表达的LTP的幅度。另一方面，NT-3和NGF没有这些作用。用抗BDNF抗体对切片进行免疫组织化学染色显示，外源性BDNF在应用后约5分钟内渗透到整个切片中。BDNF的作用被用TrkB-IgG融合蛋白（一种BDNF清除剂）预孵育切片或共同应用K252a（一种受体酪氨酸激酶抑制剂）所阻断。TrkB-IgG或K252a本身完全阻断了LTP，这表明内源性BDNF或另一种TrkB配体在发育中的视觉皮层的LTP中起作用。
